The expression of 5 antigens specific for adult intestinal crypt cells and defined by monoclonal antibodies prepared to surface membrane components of the human colon tumor cell line CaCo-2 was studied during fetal and postnatal development of Sprague-Dawley rat small and large intestines. In the small intestine, all epithelial cells were stained during fetal life; antigen distribution became restricted to the crypt and lower villus cells in suckling animals and to the crypt cells after weaning. In the colon, these antigens could be detected only during a short period of development, comprising the last 3-4 days of fetal life and the first 8-10 days after birth. Expression of the antigens defined by this group of antibodies was investigated in rat intestinal tumors induced by 1,2-dimethylhydrazine (CAS: 540-73-8) and in normal and diseased human colons. In rats, these antigens were detected in all poorly and moderately differentiated adenocarcinomas of the small and large intestines. In most specimens, antigen distribution was not uniform; intensely stained areas were surrounded by completely negative tumor regions. Antigen expression was less intense in well-differentiated tumors, and about half of the tumors were negative for antigen expression. A similar pattern of expression of these antigens was observed in all human colonic adenocarcinomas examined; all samples of normal colon, benign polyps, and inflammatory bowel diseases examined were negative. These results suggest that this group of monoclonal antibodies recognizes oncofetal rat antigens expressed in chemically induced rat intestinal tumors and human colonic adenocarcinomas.